A Long Term Follow-up Study up to 4 Years After Study Vaccination to Assess Immunogenicity and Safety of the Investigational Vaccine in Adults

NCT03201211 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2049132016-004248-13
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this long-term follow-up of a Phase I study is to evaluate the kinetics of the antibody response to NTHi-Mcat antigens and long-term safety, in subjects aged between 50-71 years at the time of enrolment in the NTHi-Mcat-001 study. These subjects were previously exposed to two adjuvanted formulations of the NTHi-Mcat vaccine administered according to a 0, 2 months schedule in the NTHi-Mcat-001 (201281) study. The subjects that had received saline placebo controls will also be included in this follow-up study to make comparisons with the investigational vaccines. No vaccinations will be administered in this trial.

Conditions

Respiratory Disorders

Keywords

Safety; Immunogenicity

Outcome Measures

Primary Outcomes (24)

• Anti-Protein D (PD) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted geometric mean concentration (GMC) and their 95% confidence interval (CI) was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the enzyme-linked immunosorbent assay (ELISA) anti-PD assay was 153 ELISA unit per millilitre (EU/mL).

  At Month 20

• Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.

  At Month 26

• Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.

  At Month 32

• Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.

  At Month 38

• Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.

  At Month 44

• Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.

  At Month 50

• Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.

  At Month 20

• Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.

  At Month 26

• Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.

  At Month 32

• Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the F13ELISA anti-PE assay was 8 EU/mL.

  At Month 38

• Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.

  At Month 44

• Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.

  At Month 50

• Anti-type IV Pili Subunit (PilA) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.

  At Month 20

• Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.

  At Month 26

• Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.

  At Month 32

• Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.

  At Month 38

• Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.

  At Month 44

• Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.

  At Month 50

• Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.

  At Month 20

• Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.

  At Month 26

• Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.

  At Month 32

• Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.

  At Month 38

• Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.

  At Month 44

• Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

  Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.

  At Month 50

Secondary Outcomes (2)

• Number of Subjects Reported With Any Serious Adverse Event (SAE)

  From first visit (Month 20) up to study conclusion (Month 50)

• Number of Subjects Reported With Any Potential Immune-mediated Disease (pIMD)

  From first visit (Month 20) up to study conclusion (Month 50)

Study Arms (3)

10-10-10-AS

EXPERIMENTAL

Subjects who received two doses of the AS01E adjuvanted GSK Biologicals' NTHi-Mcat investigational vaccine, containing 10µg of PD, PE-PilA and UspA2, and administered at Month 0 and Month 2 in NTHi-Mcat-001 study (NCT02547974), and were enrolled in the study.

Biological: Blood sampling; Biological: GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, PE-PilA and UspA2.

10-10-3-AS

EXPERIMENTAL

Subjects who received two doses of the AS01E adjuvanted GSK Biologicals' NTHi-Mcat investigational vaccine, containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2, and administered at Month 0 and Month 2 in NTHi-Mcat-001 study (NCT02547974), and were enrolled in the study.

Biological: Blood sampling; Biological: GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2.

PLACEBO

PLACEBO COMPARATOR

Subjects who received two doses of placebo (saline solution), administered at Month 0 and Month 2 in NTHi-Mcat-001 study (NCT02547974) and were enrolled in the study.

Biological: Blood sampling; Drug: Placebo

Interventions

Blood sampling BIOLOGICAL

A volume of approximately 20 mL of whole blood should be drawn from each subject, at each study visit, for antibody determination and assay validation/development.

10-10-10-AS; 10-10-3-AS; PLACEBO

GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, PE-PilA and UspA2. BIOLOGICAL

2 doses, not administered as part of this study but administered at Day 0 and Day 60 during STEP 2 of NTHi Mcat-001 (201281 - NCT02547974) study, to subjects who were then enrolled in this study. Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

10-10-10-AS

GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2. BIOLOGICAL

2 doses, not administered as part of this study but administered at Day 0 and Day 60 during STEP 2 of NTHi Mcat-001 (201281 - NCT02547974) study, to subjects who were then enrolled in this study. Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

10-10-3-AS

Placebo DRUG

2 doses, not administered as part of this study but administered at Day 0 and Day 60 during STEP 2 of NTHi Mcat-001 (201281 - NCT02547974) study, to subjects who were then enrolled in this study. Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

PLACEBO

Eligibility Criteria

• Age: 51 Years - 73 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who previously participated in STEP 2 of study NTHi-Mcat-001 (201281), and performed the last study visit (Month 14) and received the 2 study vaccinations.
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. return for follow-up visits). And subjects' Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
• Written informed consent obtained from the subject/ LAR(s) of the subject prior to performance of any study specific procedure.

You may not qualify if:

• Use of any investigational or non-registered product (drug or vaccine) during the period starting 30 days before the first follow-up study visit (Month 19 to Month 20), or planned use during the study period.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since the end of the NTHi-Mcat-001 study. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first follow-up visit or planned administration during the study period.
• Current alcoholism and/or drug abuse.
• Has significant disease (including significant neurological or psychological disorders), in the opinion of the investigator, likely to interfere with the study and/or likely to cause death within the study duration.
• Any other condition that the investigator judges may interfere with study findings.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

MeSH Terms

Conditions

Respiration Disorders

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 28, 2017
• Study Start: June 22, 2017
• Primary Completion: March 19, 2020
• Study Completion: March 19, 2020
• Last Updated: April 8, 2021
• Results First Posted: April 8, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (3)